Peptidase M1, membrane alanine aminopeptidase, N-terminal (IPR014782)

Short name:
Peptidase_M1_N

Domain relationships

None.

Description

Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role.
Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [PMID: 7674922]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [PMID: 7674922].

This group of metallopeptidases belong to the MEROPS peptidase family M1 (clan MA(E)), the type example being aminopeptidase N from Homo sapiens (Human). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.

Membrane alanine aminopeptidase (EC:3.4.11.2)
is part of the HEXXH+E
group; it consists entirely of aminopeptidases, spread across a wide
variety of species [PMID: 7674922]. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4
to form an inflammatory mediator [PMID: 7674922]. This hydrolase has been shown to
have aminopeptidase activity [PMID: 2244921], and the zinc ligands of the M1 family
were identified by site-directed mutagenesis on this enzyme [PMID: 7674922] CD13 participates in trimming peptides bound to MHC class II molecules [PMID: 8691132] and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils [PMID: 8627182]. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory
tract infections.